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Diphenhydramine: Uses, Dosage & Side Effects
Diphenhydramine is a first-generation antihistamine used to treat allergies, short-term insomnia, and motion sickness.
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Diphenhydramine is a first-generation antihistamine used to treat allergies, short-term insomnia, and motion sickness.
What is Diphenhydramine?
Diphenhydramine is a first-generation antihistamine that has been used in medicine since the 1940s. It works by blocking histamine H1 receptors in the body, preventing histamine – a key chemical mediator of allergic reactions – from triggering its typical effects. In addition to its antiallergic properties, diphenhydramine has notable sedating (sleep-inducing) and antiemetic (anti-nausea) effects.
Indications – When is Diphenhydramine Used?
Diphenhydramine is used for a variety of medical purposes:
- Allergic reactions: Treatment of hay fever, hives (urticaria), allergic itching, and mild allergic skin reactions.
- Short-term insomnia: Temporary relief of difficulty falling or staying asleep, due to its sedating properties.
- Motion sickness and nausea: Prevention and treatment of kinetosis (motion sickness), nausea, and vomiting.
- Common cold symptoms: Relief of runny nose and sneezing associated with the common cold.
- Pruritus: Relief of itching from various causes, including insect bites.
Mechanism of Action
Diphenhydramine exerts its effects primarily through three mechanisms:
Histamine H1 Receptor Blockade
By competitively blocking histamine H1 receptors, diphenhydramine prevents histamine from triggering typical allergic responses such as itching, redness, swelling, and increased mucus production.
Central Nervous System Sedation
Because diphenhydramine readily crosses the blood-brain barrier, it produces significant sedation. It also blocks muscarinic acetylcholine receptors (anticholinergic effect), as well as serotonin and alpha-adrenergic receptors, contributing to its sleep-inducing properties.
Antiemetic Effect
The antiemetic effect (reduction of nausea and vomiting) results from blockade of histamine and acetylcholine receptors in the vestibular system and the vomiting center of the brain.
Dosage and Administration
Dosage depends on the indication, age, and individual tolerability. Typical adult doses include:
- Allergy treatment: 25–50 mg orally every 4–6 hours (maximum daily dose: 300 mg)
- Insomnia: 25–50 mg orally 30 minutes before bedtime
- Motion sickness: 25–50 mg orally 30 minutes before travel
Diphenhydramine is available in multiple formulations including tablets, capsules, liquid, and topical creams. It is contraindicated in children under 2 years of age, and caution is strongly advised in elderly patients.
Side Effects
Diphenhydramine can cause a range of side effects, particularly due to its anticholinergic properties:
- Common: Drowsiness, dizziness, dry mouth, constipation, urinary retention
- Occasional: Blurred vision, rapid heartbeat (tachycardia), confusion (especially in elderly patients)
- Rare: Paradoxical excitation (particularly in children), low blood pressure, allergic reactions
Due to risks of cognitive impairment and falls, diphenhydramine is classified as a potentially inappropriate medication for older adults by the American Geriatrics Society Beers Criteria.
Interactions and Contraindications
Diphenhydramine should not be taken, or used only under medical supervision, in the following situations:
- Combination with other central nervous system depressants (alcohol, benzodiazepines, opioids) – increased sedation risk
- MAO inhibitors – risk of serious interactions
- Narrow-angle glaucoma
- Enlarged prostate with urinary retention
- Pregnancy and breastfeeding (only after medical consultation)
References
- Simons, F.E.R. & Simons, K.J. – Histamine and H1-antihistamines: celebrating a century of progress. Journal of Allergy and Clinical Immunology, 128(6), 1139–1150 (2011). PubMed PMID: 22075282.
- American Geriatrics Society 2023 Beers Criteria Update Expert Panel – American Geriatrics Society 2023 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society, 71(7), 2052–2081 (2023).
- World Health Organization (WHO) – Model Formulary 2008. Section 3: Antiallergics and medicines used in anaphylaxis. WHO Press, Geneva.
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